Could a genetic cholesterol control protect some people from dementia?

The more information about cholesterol's complex health role that comes to light, the more curious are the ways it seems to be important.

A growing body of research has noted the substance's importance in the brain (which holds about a quarter of the body's total cholesterol). Now, a new study adds another layer of understanding to the changing conception of this lipid. A common alteration in the cholesteryl ester transfer protein gene (CETP), which helps to control the size of cholesterol particles in the body, has been shown to slow subjects' rate of dementia and protect against Alzheimer's disease, researchers have found.

A swap of one amino acid (isoleucine) for another (valine) in CETP meant that individuals had "significantly slower memory decline," the researchers reported in a paper published online January 12 in JAMA, The Journal of the American Medical Association. In fact, cognitive decline occurred about 51 percent more slowly in those with valine alleles than those with isoleucine. The valine allele also appeared to protect against getting Alzheimer's disease.

"More specifically, those participants who carried two copies of the favorable CETP variant had a 70 percent reduction in their risk for developing Alzheimer's disease compared with participants who carried no copies of this gene variant," Amy Sanders, a neurologist at the Einstein College of Medicine in New York and lead study author, said in a prepared statement.

The results are preliminary, the authors reported, owing in part to the relatively small study population (523 adults aged 70 or older living in the Bronx), with 40 of them developing dementia during the course of the multi-year study.

The same genetic marker had previously been pegged by some of the same researchers, at Einstein, as an indicator of overall longevity in studies of long-living Ashkenazi Jews.

Investigations into markers for dementia and Alzheimer's risk have turned up one quite convincing candidate: apolipoprotein (APOE), which "has been conclusively associated with increased genetic susceptibility for the most common dementia," the authors of the new paper noted. So news of a genetic protector, even if preliminary, will likely be welcome news. "Most work on the genetics of Alzheimer's disease has focused on factors that increase the danger," Richard Lipton, vice chair of Einstein's Department of Neurology and senior author of the study, said in a prepared statement. "We reversed this approach…and instead focused on a genetic factor that protects against age-related illnesses."

This association of a cholesterol regulator with cognitive health fits in with other similar discoveries. "Growing evidence posits a mechanistic pathway linking cerebral cholesterol metabolism and [Alzheimer's disease] pathology," the authors wrote. "An association between CETP status and cognition and dementia is biologically plausible because other genes involved in lipid metabolism, including APOE, are associated with dementia risk."

Work is already under way to develop drugs that alter CETP function in the interest of helping those with heart disease, noted Lipton, who said he was hopeful that some of the cognitive benefits shown in this study might also be mimicked through new CETP-based therapies.

Image courtesy of iStockphoto/lisafx

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